Patients suffering from chronic ulcers and particularly diabetic ulcers are at high risk for local and systemic infections. In the frequent events of leg and foot ulcers, these patients are also at risk of structural foot deformity, limited joint mobility and amputation. Treatments for infected ulcers include glycemic control, systemic antibiotics and meticulous wound care, mainly debridement of necrotic tissue. Debridement is typically attempted by surgical methods, however, non-surgical methods including use of debriding enzymes, have been devised to avoid the blood loss and pain inherent in surgery. Furthermore, enzymatic debridement does not require exposure of the injured patient to additional trauma related to the surgical procedure and yet provides an immediate and a fast resolution of the emergency medical conditions associated with ulcers.
Debriding enzymes are also useful for treating severe skin problems, such as eczema, psoriasis and the like, and less severe skin conditions, such as wrinkles, acne and dry skin, as disclosed for example in U.S. Pat. Nos. 4,524,136; 5,439,935; 5,441,740; 5,554,366; 5,853,705 and 6,780,444. Commercial products comprising such enzymes are also available, e.g. Accuzyme® (papain) and Granulex® (trypsin), the application of which is limited for debridement of wounds.
U.S. Pat. Nos. 4,197,291; 4,226,854; 4,307,081; 4,329,430 and 5,830,739 disclose hydrolytic enzymes derived from the pineapple plant and composition comprising same. US Patent Application No. 2003/0026794 discloses methods for treating skin conditions using at least one enzyme that affects one or more particular layers of skin. The aforementioned enzymatic preparations posses limited shelf life under standard storing conditions, such as storage at room temperature.
Enzymatic compositions may be stabilized by moieties that inhibit lose of enzymatic activity during storage. For example, U.S. Pat. No. 6,692,726 discloses stable oral compositions comprising enzymes, cetyl pyridinum chloride and a reducing agent which confer stability to the compositions. Typically, such additives are suitable only for particular enzymes and moreover to particular uses of said enzymes.
Methods and apparatus for applying enzymatic composition onto a wound are taught in WO03/011369, US 2004/0186421 and WO2005/070480 of the inventor of the present invention, all of which are incorporated in their entirety by reference, as is fully set forth herein. These applications disclose apparatus for continuous streaming therapeutic solutions, particularly solutions comprising proteases as the active ingredient, over a wound such as an ulcer.
It was further shown by the inventor of the present invention that applying a stream of active proteolytic enzyme for a few hours, through and over the wound area provides an effective debridement (Freeman et al., Wound 16:201-205, June 2004). Similar treatment with a buffer solution devoid of enzymes was found to be ineffective. Furthermore, treatment with a static (non-flowing) composition of enzymes for a similar time period had no effect.
There is an unmet need for enzymatic compositions comprising debriding enzymes and having long shelf life while maintaining effective debriding activity. Advantageously, such compositions should be easy to use and thus can be applied by any user and not necessarily by a health-care professional.